AB0173 MUCOSAL IMMUNE DEFENCE POLYMORPHISMS: RELEVANT PLAYERS IN IGA VASCULITIS?
Authors: V. Pulito-Cueto, S. Remuzgo Martinez, F. Genre Romero, B. Sevilla, N. Ortego, M. Leonardo, A. Peñalba, J. Narváez, L. Martín-Penagos, L. Belmar-Vega, C. Gomez-Fernandez, M. Sebastián Mora-Gil, L. Caminal Montero, P. Collado, D. De Argila, P. Rodriguez-Jimenez, E. F. Vicente-Rabaneda, E. Rubio-Romero, M. Leon Luque, J. M. Blanco-Madrigal, E. Galíndez-Agirregoikoa, J. Martin Ibanez, S. Castañeda, M. A. González-Gay, R. Blanco, R. López-Mejías
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Several mucosal immune defence polymorphisms have an impact on IgA production by plasma cells in the mucosa [1]. In this regard, these genetic variants have been previously reported as susceptibility <i>loci</i> for IgA nephropathy [1]. Given the pathophysiological similarities described between IgA nephropathy and Immunoglobulin-A vasculitis (IgAV) [2, 3], mucosal immune defence polymorphisms may also be implicated in the pathogenesis of IgAV. <h3>Objectives</h3> To determine whether mucosal immune defence polymorphisms represent novel genetic risk factors for the pathogenesis of IgAV. <h3>Methods</h3> 6 mucosal immune defence polymorphisms previously described as susceptibility <i>loci</i> for IgA nephropathy (<i>ITGAM-ITGAX</i> rs11150612, <i>VAV3</i> rs17019602, <i>CARD9</i> rs4077515, <i>CFHR3.1-del</i> rs6677604, <i>DEFA</i> rs2738048 and <i>HORMAD2</i> rs2412971) were selected. These 6 genetic variants were genotyped in 300 unrelated Caucasian patients with IgAV (the largest series of Caucasian IgAV patients assessed for genetic studies) and 1,012 matched healthy controls. 36.1% of the IgAV patients developed renal manifestations. <h3>Results</h3> No statistically significant differences were observed in the genotype and allele frequencies of mucosal immune defence polymorphisms when IgAV patients and healthy controls were compared (<b>Table 1</b>). Moreover, no statistically significant differences were disclosed in the genotype and allele frequencies of the 6 polymorphisms selected when patients with IgAV were stratified according to the presence/absence of renal manifestations (<b>Table 1</b>). Likewise, similar genotype and allele frequencies of these polymorphisms were disclosed in patients with IgAV stratified according to the age at disease onset and to the presence/absence of gastrointestinal manifestations. <h3>Conclusion</h3> Our results reveal that mucosal immune defence polymorphisms do not contribute to the genetic background of IgAV. <h3>References</h3> [1] Nat Genet 2014, 46, 1187-96 [2] N Engl J Med 2002, 347, 738-48 [3] N Engl J Med 2013, 368, 2402-14. <h3>Acknowledgements</h3> This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI18/00042 and PI21/00042, co-funded by European Regional Development Fund (ERDF), `Investing in your future´; VP-C: PI18/00042 from ISCIII, co-funded by ERDF; MSM-G is supported by funds of TRANSVAL22/01 from IDIVAL; RL-M: Miguel Servet type II programme fellowship from the ISCIII, co-funded by the European Social Fund (`Investing in your future´) [CPII21/00004]. <h3>Disclosure of Interests</h3> Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre Romero: None declared, Belén Sevilla: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, J. Narváez: None declared, Luis Martín-Penagos: None declared, Lara Belmar-Vega: None declared, Cristina Gomez-Fernandez: None declared, María Sebastián Mora-Gil: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Diego de Argila: None declared, PEDRO RODRIGUEZ-JIMENEZ: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Raquel López-Mejías: None declared.